SGCZ (sarcoglycan zeta) is a component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex that links the F-actin cytoskeleton to the extracellular matrix [UniProt]. This structural role is critical for maintaining striated muscle membrane stability. Beyond its established sarcomeric function, SGCZ has emerged as a locus associated with multiple disease phenotypes in genome-wide association studies. SGCZ variants are linked to prediabetes status change, with robust meta-analysis support across the Atherosclerosis Risk in Communities and Framingham Heart Study cohorts 1. Additionally, a genomic locus in SGCZ was associated with changes in best-corrected visual acuity in patients with macular edema treated with anti-VEGF therapy 2. DNA methylation at a CpG site (cg03748458) annotated to SGCZ showed association with total nicotine equivalents in smokers, suggesting epigenetic responsiveness to tobacco exposure 3. Notably, genomic deletions in SGCZ increased risk for arsenic-induced skin lesions, with stronger effects in females 4, and a SGCZ nonsense mutation (p.Q134X) was identified as a potential contributor to clinical heterogeneity in a hypertrophic cardiomyopathy family 5. However, SGCZ mutations do not appear to contribute to myoclonus dystonia genetic heterogeneity 6.