TTC5 (tetratricopeptide repeat domain 5) is a multifunctional cofactor that regulates diverse cellular processes including tubulin homeostasis, transcriptional control, and stress responses. Its primary function involves tubulin autoregulation, where TTC5 recognizes nascent tubulin polypeptides at translating ribosomes and recruits the CCR4-NOT deadenylase complex via SCAPER to trigger tubulin mRNA degradation when free tubulin levels are excessive 1. Under normal conditions, soluble αβ-tubulins sequester TTC5 through its flexible C-terminal tail, preventing inappropriate activation 2. The CARM1-PI3KC2α axis further regulates TTC5 activity, with PI3KC2α methylation by CARM1 controlling TTC5 release and tubulin autoregulation initiation 3. Beyond tubulin regulation, TTC5 functions as a stress-responsive transcriptional cofactor, activating p53 pathways while inhibiting AP-1 transcription, leading to cell cycle arrest and apoptosis 4. TTC5 also stabilizes glucocorticoid receptors and modulates their transcriptional activity in a stress-dependent manner 5. Clinically, biallelic TTC5 mutations cause a severe neurodevelopmental disorder characterized by intellectual disability, cerebral atrophy, microcephaly, growth retardation, and distinctive facial dysmorphism 67. The syndrome's severity reflects TTC5's critical roles in brain development and cellular homeostasis.