Estrogen is a key hormone involved in the development and homeostasis of several tissue types in both males and females. By binding estrogen receptors, estrogen regulates essential functions of gene expression, metabolism, cell growth, and proliferation by acting through cytoplasmic signaling pathways or activating transcription in the nucleus. However, disruption or dysregulation of estrogen activity has been shown to play a key role in the pathogenesis and progression of many diseases. This review will expatiate on some of the unconventional roles of estrogen in homeostasis and disease