Phb1, or prohibitin 1, is a multifunctional chaperone/scaffold protein. It is an inner mitochondrial membrane protein that plays a crucial role in maintaining mitochondrial integrity and function, and is involved in multiple cellular processes, including innate immune responses, cell proliferation, and apoptosis. It has been associated with pathways such as the mitochondrial permeability transition pore (mPTP)-related regulation and androgen receptor (AR) signaling [1,2].

Loss-of-function studies have provided significant insights into Phb1's role. In myeloid-specific Phb1 KO (Phb1MyeKO) mice, macrophages show increased interleukin-1β (IL-1β) levels and cytoplasmic release of mtDNA, indicating that Phb1 deficiency leads to enhanced inflammatory responses [1]. In PHB1 KO mice, they are intolerant of lipopolysaccharide shock, further demonstrating Phb1's role in innate immunity [1]. In the context of cancer, PHB1 is upregulated in castration-resistant prostate cancer (CRPC), and its knockdown in vitro and in vivo experiments shows that it promotes castration resistance, suggesting its oncogenic role in CRPC [2].

In conclusion, Phb1 is essential for maintaining mitochondrial function and regulating inflammatory responses and cancer-related processes. The use of Phb1 KO/CKO mouse models has been instrumental in revealing its role in innate immunity and cancer, providing valuable insights into potential therapeutic targets for diseases such as neonatal sepsis and CRPC.