CLMN (calmin) is a multifunctional protein that serves as an ER-actin tether and regulates cell cycle progression. The protein localizes to focal adhesions adjacent to ER tubules, where it functions as an actin-binding protein that tethers the endoplasmic reticulum to the actin cytoskeleton 1. CLMN plays a crucial role in cell migration by facilitating focal adhesion disassembly and actin dynamics, with depletion leading to impaired cell movement and altered calcium signaling near ER-actin interfaces 1. In neuronal development, CLMN is regulated by all-trans retinoic acid and promotes cell cycle exit through G1/S arrest, increasing p21(Cip1) and decreasing cyclin D1 protein levels 2. This cell cycle regulation is essential for neuronal differentiation and neurite outgrowth 2. Clinically, CLMN shows disease relevance in multiple contexts. Homozygous truncating mutations in CLMN have been identified as candidate variants in consanguineous families with neurodevelopmental disorders 3. In breast cancer, high CLMN mRNA expression correlates with improved overall survival and favorable prognosis 4. Additionally, genetic variants in CLMN are associated with statin-mediated cholesterol reduction, with rs8014194 showing genome-wide significant association with total cholesterol response 5.