FUNDC2, also known as HCBP6, is a highly conserved and ubiquitously expressed mitochondrial outer membrane protein. It plays crucial roles in multiple biological processes, associated with pathways such as ferroptosis, mitochondrial fusion, platelet activation, and the AKT signaling pathway. Its functions are of great significance in various physiological and pathological conditions [1,2,3,5].

In gene knockout studies, FUNDC2-knockout mice have provided valuable insights. For instance, knockout of FUNDC2 protected mice from doxorubicin-induced cardiac injury by preventing ferroptosis, suggesting its role in this form of cell death [1]. In liver tumorigenesis, knockdown of FUNDC2 in mice inhibited liver tumorigenesis as it promotes liver tumorigenesis by inhibiting MFN1-mediated mitochondrial fusion [2]. In platelets, FUNDC2-knockout mice displayed deficiency in haemostasis and thrombosis, indicating its positive regulation of platelet functions via the AKT/GSK-3β/cGMP axis [3]. In triple-negative breast cancer, silencing FUNDC2 in TNBC cells significantly reduced cell proliferation, migration and invasion, and suppressed tumor growth in mouse xenografts [4].

In conclusion, FUNDC2 is a key mitochondrial protein involved in diverse biological functions. Studies using KO mouse models have revealed its roles in diseases like doxorubicin-induced cardiomyopathy, liver tumorigenesis, platelet-related disorders, and triple-negative breast cancer, highlighting its potential as a therapeutic target in these disease areas.