STAC3, an adaptor protein, is essential for excitation-contraction (EC) coupling in skeletal muscles. It interacts with the voltage-sensor CaV1.1 of EC-coupling and is involved in pathways related to muscle contraction. Mutations in STAC3 can lead to congenital myopathies, highlighting its biological importance in muscle development and function. Genetic models, such as gene knockout mouse models, are valuable for studying STAC3's role [2,4,6].

In a study on STAC3-related congenital myopathy, a homozygous missense variant (c.851G > C; p.Trp284Ser) in STAC3 was found to segregate with Native American myopathy (NAM) in the Lumbee tribe and was also identified in Comorian patients, suggesting a founder effect [1]. STAC3 disorder, characterized by congenital myopathy, hypotonia, and other anomalies, was found to be a common cause of congenital hypotonia in Southern African patients, with a high frequency of the c.851G > C variant [3]. STAC3 knockdown promoted myoblast differentiation into myotubes, while overexpression inhibited this process, indicating its role in preventing premature myoblast differentiation [5].

In conclusion, STAC3 is crucial for skeletal muscle EC-coupling and muscle development. Its mutations are associated with congenital myopathies and related disorders. Studies using gene-based models, like the ones mentioned, have revealed its role in muscle-related biological processes and disease conditions, contributing to our understanding of these muscle-associated pathologies.