Slc22a18, solute carrier family 22 member 18, is an orphan transporter whose endogenous substrate remains unknown. It has been associated with lipid metabolism and tumor-related processes. In lipid metabolism, it may be involved in pathways regulating triglyceride synthesis and degradation. In tumors, its chromosomal location at 11p15.5 and aberrant expression in various cancers suggest it could be a tumor-related gene, potentially acting as a tumor suppressor [4,5,6,7,8,9]. Genetic models, such as knockout mice, are valuable for studying its functions.

Slc22a18 knockout mice grew normally but showed decreased hepatic triglyceride content under refeeding conditions, reduced epididymal fat mass, and lower liver weight with leptin deficiency, indicating its positive role in lipid accumulation in vivo [1]. In HepG2 cells, knockdown of SLC22A18 impaired lipid metabolism, suppressed lipid degradation, and increased cell invasiveness [3]. In colorectal cancer, SLC22A18 knockdown led to oxaliplatin resistance, and its low expression was correlated with worse survival, with ERK activation involved in this resistance mechanism [2]. Missense variants of SLC22A18 in colon cancer cells led to higher cell proliferation, migration, and invasion compared to the wild-type [7].

In conclusion, Slc22a18 plays a significant role in lipid metabolism, promoting fat accumulation in vivo. In the context of diseases, it shows potential as a biomarker and is involved in tumor-related processes such as tumor suppression, cell invasion, and drug resistance. Studies using knockout mouse models and cell-based knockdown experiments have been crucial in revealing these functions, providing insights into the underlying biological mechanisms and potential therapeutic targets for lipid-related disorders and cancers.