Ahcyl1, also known as adenosylhomocysteinase like 1 or S-adenosylhomocysteine hydrolase-like protein 1 (IRBIT), is a member of the AHCY family. It functions as a SAH sensor, interacting with SAH and PIK3C3 to inhibit autophagy in an MTORC1-independent manner [1]. It also plays roles in regulating cell survival/death, stemness capacity, and the host adaptive response to the tumor microenvironment, and is involved in processes like ER calcium homeostasis regulation [1,3,5].

In cancer research, Ahcyl1 shows differential expression in colorectal cancer (CRC), with deletion associated with shorter survival, weaker immune cell recruitment, and reduced response to immunotherapy [2]. In NRAS-mutated melanoma, Ahcyl1 is selectively upregulated and crucial for cell proliferation and tumor growth, as its deficiency leads to decreased ER calcium levels, UPR activation, and apoptosis [3]. In non-small cell lung cancer (NSCLC), Ahcyl1 is a negative regulator of tumorigenesis, and its silencing enhances stem-like properties and tumorigenicity [4]. In addition, Ahcyl1 mediates the tumor-promoting effect of PREX2 in NSCLC by enhancing PREX2's GEF activity [6].

In conclusion, Ahcyl1 is a multifunctional gene involved in autophagy, calcium homeostasis, and cancer-related processes. Its study in KO/CKO mouse models and other loss-of-function experiments has provided insights into its role in cancer, suggesting it could be a potential biomarker and therapeutic target for various cancers including CRC, melanoma, and NSCLC [1-4,9].