Prohibitin (PHB) is overtly conserved evolutionarily and ubiquitously expressed protein with pleiotropic functions in diverse cellular compartments. PHB is a ubiquitous protein that is mainly localized in the inner mitochondrial membrane and exerts various mitochondrial functions. PHB may be a substrate of poly-ubiquitin to regulate the ubiquitination of mitochondria and even subsequent elimination during P. esculenta spermiogenesis, and it has a potential role in guaranteeing the maternal inheritance of mitochondria. PHB might play important roles during spermatogenesis and oogenesis by regulating mitochondrial activities. There are several studies reported to understand and decipher PHB's role in diseases and/or cancers of ovary, lung, stomach, thyroid, liver, blood, prostate, gastric, esophagus, glioma, breast, bladder, etc. where PHB is shown to act through mechanisms by acting as an oncogene, tumor suppressor, antioxidant, antiapoptotic, in angiogenesis, autophagy, etc.