HSF4 (heat shock transcription factor 4) is a transcriptional activator that plays crucial roles in lens development and cellular stress responses 1. The protein functions as a DNA-binding transcription factor that activates expression of crystallin genes and beaded filament structural proteins essential for lens fiber cell differentiation 1. HSF4 binds to various genomic regions including introns and distal parts of protein-coding genes, often co-occupying sites with HSF1 and HSF2 2. The protein regulates gene expression during lens development when HSF1 and HSF2 expression decreases, and induces demethylated status of histone H3K9 on binding regions 2. Unexpectedly, HSF4 is required for induction of non-classic heat shock genes in response to heat stress, facilitating HSF1 binding through chr16 modification 2. Mutations in HSF4 are associated with congenital and age-related cataracts, with missense mutations causing loss of DNA-binding activity and subsequent loss of lens protein gene expression 13. HSF4 deficiency increases secretion of small extracellular vesicles through upregulation of chaperone-mediated autophagy, potentially contributing to cataract development 4. Beyond ocular function, HSF4 has been implicated in colorectal cancer progression and prostate cancer therapy resistance 56.