Rb1cc1, also known as FIP200, is an essential macroautophagy/autophagy protein that plays a crucial role in a variety of biological and disease processes through its canonical autophagy-dependent and-independent functions. It is a subunit of the ULK1 complex in more complex eukaryotes and is proposed to be a functional homolog of yeast Atg17 and Atg11 scaffolding proteins. Rb1cc1 is involved in autophagy-related pathways such as autophagy initiation, autophagosome formation, and mitophagy [2,3,4,5].

Muscle-specific rb1cc1-conditional knockout (cKO) mice showed features of autophagic vacuolar myopathy with ubiquitin+ SQSTM1+ deposits, as well as TARDBP/TDP-43+ pathology, highlighting its role in maintaining muscle homeostasis [6]. In tumour cells, lipid ROS upregulates Rb1cc1, and its nuclear translocation at Ser537 phosphorylation is essential for sensitising ferroptosis. Nuclear Rb1cc1 recruits ELP3 to enhance H4K12Ac histone modifications within enhancers related to ferroptosis, stimulating the transcription of ferroptosis-associated genes and ultimately suppressing liver tumourigenesis in mice [1].

In conclusion, Rb1cc1 is vital for autophagy-related functions and muscle homeostasis. Its role in sensitising tumour cells to ferroptosis suggests potential therapeutic implications in cancer treatment. Studies using cKO mouse models have significantly contributed to understanding its functions in muscle-related pathologies and tumour suppression.