RTTN (rotatin) is a centrosomal protein essential for centriole biogenesis and neuronal development. Mechanistically, RTTN directly interacts with STIL and acts downstream of STIL-mediated centriole assembly, serving as an upstream effector of CEP295 to load distal-half centriolar proteins 1. During mitosis, RTTN regulates proper spindle positioning and normal mitotic progression; its depletion causes γ-tubulin dispersal, multipolar spindles, and impaired NuMA localization 2. Additionally, RTTN plays a previously unrecognized role in centrosome reorganization during cardiomyocyte maturation, where it facilitates perinuclear repositioning of centrosomal components 3. In neural development, RTTN regulates neural stem cell polarization and rosette formation in cortical organoids 4, and interacts with neuronal myosin heavy chains to support neuronal migration 5. Biallelic RTTN mutations cause autosomal recessive primary microcephaly characterized by intellectual disability, short stature, and cortical malformations including polymicrogyria and lissencephaly 5. Disease severity correlates with residual RTTN protein function rather than mRNA levels 5. Pathogenic variants induce severe mitotic failure, centrosome amplification, aneuploidy, and neuronal progenitor depletion 5. Recently, RTTN mutations were identified in infantile dilated cardiomyopathy 3 and fetal ventriculomegaly 6, expanding the clinical spectrum. The naturally occurring microcephaly-associated mutant RTTN (A578P) exhibits reduced STIL binding affinity and blocks centriole assembly 1.