TBCE (tubulin folding cofactor E) is a molecular chaperone essential for tubulin heterodimer assembly and cytoskeletal organization. TBCE functions in the post-chaperonin tubulin folding pathway, regulating the second step of tubulin maturation and controlling heterodimer dissociation 1. The protein is critical for organizing the microtubule cytoskeleton, mitotic spindle formation, and maintaining neuronal microtubule networks. TBCE is differentially localized in gametes: in sperm it concentrates in the middle region and tail, while in oocytes it distributes cytosolically 1. Pathogenic TBCE variants cause three autosomal recessive neurodevelopmental disorders: Kenny-Caffey syndrome type 1 (KCS1), Hypoparathyroidism-retardation-dysmorphism syndrome, and progressive encephalopathy with amyotrophy and optic atrophy 2. KCS1 presents with short stature, hypoparathyroidism, electrolyte disturbances, dental abnormalities, ocular abnormalities, and intellectual disability as distinguishing features 3. TBCE mutations cause microtubule structural disturbances; in motor neurons this triggers retrograde degeneration and apoptosis 4, while in the cochlea mutations cause auditory nerve dysfunction and hair cell loss with progressive hearing loss 5. Recent studies reveal phenotypic expansion including rigid spine, eosinophilia, and testicular failure, with some variants producing partially functional proteins through alternative translation mechanisms 62. Beyond neurological roles, TBCE deficiency promotes vascular dysfunction through endoplasmic reticulum stress 7.