Among the HSFs (HSF1–HSF4), HSF1 and HSF2 are most the studied factors due to their co-expression in most tissues and cell lines.4, 5 HSF1 is the main factor responsible for the HSF-HSE signal upon heat shock, whereas HSF2 is more prominently activated during mouse heart development.6, 7 Early findings indicated that HSF1 was the cardioprotective factor during heart failure.8 However, the role of HSF2 in heart failure has not been extensively investigated. The gene discussed is HSF4; the disease is heart failure.