The extrinsic muscles, of which the genioglossus muscle is part of it, determine the movement of the tongue, while the intrinsic muscles determine the shape of the tongue.  

Checking the shape of the tongue and its movement can give many clinical signals during the evaluation. 

The ability to lower the tongue correctly allows better use of the vocal cords, for example, when using a wind instrument (clarinet).The color of the tongue requires evaluation. According to recent studies, for example, a yellow or bluish tongue may indicate the presence of type II diabetes mellitus.

The genioglossus muscle will be negatively affected by the presence of pathologies, both of the oral cavity, and systemic diseases. For example, constant hypoxia (during sleep) can alter muscle metabolism. Type 17 microRNAs (miRNAs-17) helps the genioglossus muscle satellite cells repair muscle tissue and maintain an efficient mitochondrial membrane potential. Overnight hypoxia due to airway obstruction (COPD or OSAS, or CHF) causes a decline in miRNAs-17, leading to functional muscle weakness.

There are multiple physiological variants associated with the genioglossus muscle, one being food manipulation. The tongue is required to manipulate food around the mouth; the movement of the food within the mouth is necessary to form what is called a bolus. The bolus is what is swallowed and consumed for digestion later by the stomach. To swallow the bolus, the tongue must elevate and push posteriorly to ensure the bolus makes it past the tonsils.[9][10] In some people, the genioglossus muscle is shorter than others, and this causes difficulty swallowing as the tongue is unable to elevate entirely and push the food posteriorly.[9][11] This issue can lead to food that does not form a bolus for swallowing, which could lead to choking if the food is large enough.[12]

As stated above, some people have different length genioglossus, and if the genioglossus develops but does not develop properly and is shorter, than it should be, this can lead to speech problems. The tongue is unable to elevate or protrude, and this makes it difficult for people who suffer from this to pronounce certain words that contain the letter S in them.[10]  The common tern for this condition is a lisp. There is not a surgical fix for this, and most people who suffer from this will go their whole lives with this speech abnormality.

A hemiglossectomy is normally completed on the lateral portion of the tongue because most cancers present in that area. The lateral portion of the tongue, if oral cancer is present, will most likely be surgically resected; this surgical resection commonly affects and inhibits the proper functioning of the tongue muscles; including the genioglossus.[12] The surgeon removes the anterior and the middle portions of the genioglossus muscles during this resection as well as other intrinsic and extrinsic tongue muscles, but the posterior portion of the muscle is only minimally affected during resection. This condition makes it difficult for patients who undergo this surgery to swallow as the genioglossus muscle functions improperly due to the resection of the anterior and middle portions of the muscle.[12][13][14]

 Genioglossus muscle advancement is a surgical approach in patients with obstructive sleep apnoea syndrome so that the tongue has difficulty remaining in a posterior position during sleep.

The genioglossus is a muscle responsible for airway dilation. When the muscle has decreased function, it can lead to airway constriction/obstruction.[15] This situation becomes important during sleep as a patient will have multiple airway collapses while sleeping, leading to hypoxemia during sleep, which has shown to increase the risks of strokes and sudden cardiac death.[15] How this occurs is that during REM (rapid eye movement) sleep the genioglossus muscle tends to relax and it is during this relation that the obstructive sleep apnea can occur as the muscle is no longer participating in airway dilation making the airway more prone to constriction/obstruction.[16] The way to resolve this problem is for patients who suffer from this to use a continuous positive airway pressure, also known as a CPAP while sleeping, which will allow for constant airway dilation and prevention of obstructive sleep apnea.[15] The obstructive sleep apnea has commonly been shown to occur following a uvulopalatopharyngoplasty, also referred to as a UPPP.[17]

Another clinical significance of the genioglossus muscle is that it can help test the functioning of the hypoglossal nerve. The patient will be asked by a physician to stick out their tongue. Damage to the hypoglossal nerve will cause the tongue to deviate to the side of the neural lesion, allowing the physician to know which peripheral portion of the hypoglossal nerve is damaged, right or the left.

Myofunctional therapy is essential for restoring the function of the genioglossus muscle after surgery or trauma or nerve injury.

The literature shows that a cervical trauma (whiplash) can negatively influence the function of the tongue and osteopathic treatment can restore the lingual function.

To assess the tension and tone of the tongue, it is possible to use a glove and a gauze and to pull the tongue out (passive protrusion), or put a finger to the side, above and below the tongue when it is protracted, to check its strength and any compensations (with the neck, eyes, or the jaw).