TAF15 (TATA-box binding protein associated factor 15) is a multifunctional RNA and DNA-binding protein that plays critical roles in transcriptional regulation and RNA metabolism. As a component of the TAF15/TBP complex, it mediates transcriptional activation by binding to single-stranded RNA sequences and participating in RNA polymerase II preinitiation complex formation 1. TAF15 functions alongside related proteins TLS and EWS as classical transcription factors while also contributing to splicing and mRNA transport processes 2. The protein regulates epithelial-mesenchymal transition and cancer metastasis through IL-6 transactivation in lung adenocarcinoma 1. Additionally, TAF15 acts as a SUMO2 E3 ligase, controlling ribosomal RNA 2'-O-methylation by regulating NOP58 sumoylation and snoRNP assembly, which enhances oncogenic protein expression in glioma stem cells 3. Importantly, TAF15 is implicated in neurodegenerative diseases, particularly frontotemporal lobar degeneration (FTLD). Recent cryo-electron microscopy studies revealed that TAF15, not FUS as previously believed, forms characteristic amyloid filaments in FTLD-FUS cases, establishing TAF15 proteinopathy as a distinct neurodegenerative mechanism 4. TAF15 also impacts MHC class II antigen presentation pathways, suggesting roles in immune system dysfunction associated with ALS 5.