TBCB (tubulin folding cofactor B) is a cytoplasmic protein that plays a critical role in tubulin biogenesis and microtubule dynamics. Structurally, TBCB contains a CAP-Gly domain and a characteristic DEI/M-COO(-) motif that mediates its autoinhibition and enables heterodimerization with TBCE 1. Primary Function: TBCB binds to α-tubulin folding intermediates after chaperonin interaction and regulates tubulin heterodimer dissociation and recycling 2. The protein localizes to spindle and midzone microtubules during mitosis and mediates microtubule dynamics through EB1 interactions 1. Mechanism: TBCB functions within a multiprotein complex with TBCE, TBCD, TBCA, and Arl2 to facilitate proper tubulin folding, dimerization, and subsequent dissociation when needed 2. When overexpressed or derepressed, TBCB promotes microtubule depolymerization 1. Disease Relevance: Heterozygous TBCB mutations cause a novel form of hereditary spastic paraparesis associated with global developmental delay and autism spectrum disorder, with reduced TBCB protein levels impairing axonal function 3. TBCB is also pathologically targeted by Salmonella effectors during bacterial infection 4 and can be stabilized by HILI in cancer cells, promoting microtubule destabilization and tumorigenesis 5. Clinical Significance: TBCB dysfunction represents an emerging neurodevelopmental disorder mechanism with high carrier frequency in specific populations, highlighting its essential role in CNS development and axonal integrity.