CCDC57 is a pleiotropic regulator of centrosome and microtubule-mediated cellular processes critical for proper cell division and ciliary function. 1 The protein localizes to the proximal end of centrioles and directly interacts with microcephaly protein CEP63, recruiting it and CEP152 to the centrosome—a function essential for centriole duplication. 1 Beyond centrosomal roles, CCDC57 independently localizes to microtubules and regulates microtubule nucleation and mitotic progression through distinct functional domains. 1 In developmental contexts, CCDC57 controls ependymal cell polarity by organizing microtubule networks and positioning ciliary basal bodies, with loss-of-function causing disorganized ciliary beating and cerebrospinal fluid flow defects. 2 The gene also regulates left-right patterning during embryogenesis; ccdc57 depletion in Xenopus causes abnormal cilia and laterality defects, while patient-derived CCDC57 variants fail to rescue ciliary function. 3 Clinically, CCDC57 dysfunction is implicated in neurodevelopmental and structural disorders: mutations associate with restless legs syndrome susceptibility, 4 adolescent idiopathic scoliosis through disrupted ependymal polarity, 2 and situs inversus via impaired left-right patterning. 3 Genetic variants also appear in genome-wide association studies of uterine leiomyomata predisposition. 5 These findings establish CCDC57 as a critical interface between centrosomal and microtubule-based mechanisms governing cell division and ciliary processes.