Ctla4, also known as cytotoxic T-lymphocyte antigen-4 or CD152, is a member of the immunoglobulin-related receptor family [2]. It plays a crucial role in T-cell immune regulation as an inhibitory receptor. Ctla4 shares common ligands (B7.1 and B7.2) with stimulatory receptor CD28, and its expression is important for the negative regulation of T-cell responses [1]. By promoting long-lived anergy in immune cells, it prevents autoimmunity and is thus involved in T-cell-mediated autoimmunity and susceptibility to autoimmune diseases [2].

Heterozygous germline variants in Ctla4, leading to haploinsufficiency, have been associated with several immunological disorders, including hypogammaglobulinemia, multi-organ autoimmunity, lymphoproliferative disorders, and enlarged lymphoid organs [5]. CTLA4-haploinsufficiency is a complex disease of immune dysregulation presenting with a broad spectrum of clinical manifestations [3]. In urothelial cancer, CTLA4 blockade in combination with anti-PD1 or anti-PDL1 therapies shows encouraging antitumour effects, potentially transforming immunologically cold tumours into hot tumours [4].

In conclusion, Ctla4 is an essential negative regulator of immune responses. Studies on Ctla4-related immunological disorders and its role in cancer treatment, such as in urothelial cancer, through model-based research, help us understand its biological functions and potential as a therapeutic target in autoimmune diseases and cancer.