ACTN3 encodes α-actinin-3, an F-actin cross-linking protein localized to the Z-disc of skeletal muscle that bundles actin filaments and anchors them to intracellular structures 1. Expression is restricted to type 2 (fast-twitch) fibers responsible for forceful, high-velocity contractions 1. A common R577X stop-codon polymorphism results in α-actinin-3 deficiency in approximately 18% of Caucasians 2, which does not cause disease but is compensated by the homologous protein α-actinin-2 2. The RR genotype associates with enhanced sprint and power performance, with elite sprint athletes showing significantly higher R allele frequencies 2. Conversely, the XX genotype may confer advantages in endurance activities through a metabolic shift toward oxidative metabolism and increased fatigue resistance 1. In aging populations, ACTN3 genotype influences muscle phenotype and bone mineral density 3, though associations with sarcopenia require further investigation 4. A recent missense variant increases filament flexibility, reducing maximal force in type IIA fibers 5. The ACTN3 R577X polymorphism also associates with joint range of motion, with XX and RX genotypes showing greater flexibility than RR 6. Gene dosage studies demonstrate that ACTN3 overexpression is detrimental to muscle function, highlighting the sensitive balance of sarcomeric protein stoichiometry 7.