OTOL1 (otolin 1) is a collagen-like scaffold protein specifically expressed in the inner ear that plays a critical role in otoconia formation and biomineralization. The protein functions by sequestering calcium ions and forming interconnecting fibrils that become incorporated into calcium carbonate crystal structures within the saccule and utricle 1. OTOL1 contains a functionally important gC1q domain responsible for trimerization and calcium binding, with natural variants in this domain significantly affecting protein stability and self-association properties 1. Mutations such as R342W induce detrimental aggregation while R402P disables trimerization, potentially compromising otoconia integrity 1. These structural disruptions may pathologically alter the otoconial membrane and impair balance sensation, increasing susceptibility to benign paroxysmal positional vertigo (BPPV) 1. Beyond inner ear function, OTOL1 has been identified as a candidate longevity gene in genome-wide association studies 2 and as a genetic locus associated with anthropometric traits including BMI in Asian populations 3, suggesting broader physiological roles. Additionally, OTOL1 variants contribute to genetic risk scores for obesity, with dietary pattern interactions modulating their phenotypic effects 4.