TAF5 is a 100-kDa subunit of TFIID, the general transcription factor essential for RNA polymerase II-dependent transcription initiation 1. TAF5 participates in two TFIID modules: TFIID-A (with TAF3 and TBP) and TFIID-B (with TAF8), and mediates contacts between TFIID and TFIIF in the pre-initiation complex 1. Structurally, TAF5 contains an N-terminal domain with conserved clefts critical for TFIID assembly and forms flexible dimers essential for complex formation 2. TAF5 belongs to a stable core-TFIID subcomplex including TAF4, TAF6, TAF9, and TAF12, present in two copies within holo-TFIID 3. Mechanistically, TAF5 alternative exon-8 inclusion is required for TFIID assembly and regulation of global gene expression 4. The chaperonin CCT provides checkpoint control of TAF5 maturation, facilitating its handover to TAF6-TAF9 for holo-TFIID formation 5. Disease relevance includes potential associations with oral squamous cell carcinomas and osteoarthritis pathogenesis 67. TAF5 functions as a critical architectural component enabling TFIID-mediated transcriptional initiation and gene expression regulation.