Ppfia4, also known as liprin-alpha-4, belongs to the PPFIA family of kinesin-cargo linkers. It consists of PFIH1-4 domains and three SAM domains. Although its exact essential function is still being explored, studies suggest it is involved in multiple cellular processes such as cell metabolism, proliferation, migration and invasion. It is associated with pathways like G-protein coupled peptide receptor activity, peroxisome proliferator-activated receptors, and hypoxia-inducible factor-1 signaling pathways [5].

In cancer research, gain-and loss-of-function studies in cell lines and mouse models have been crucial. For example, in castration-resistant prostate cancer (CRPC), knockdown of Ppfia4 in PCa cell lines and mouse models of subcutaneous xenograft showed that Ppfia4 promotes CRPC by enhancing mitochondrial metabolism through interaction with MTHFD2 [1]. In esophageal cancer cells, inhibition of Ppfia4 decreased the invasion, migration ability and glycolysis [2]. Similar results were seen in colon cancer cells where Ppfia4 knockdown reduced cell proliferation, migration, invasion and glycolysis [3]. In ovarian cancer, Ppfia4 knockdown inhibited hypoxia-induced glucose metabolic reprogramming and the migration and invasion of ovarian cancer cells [4]. In colorectal cancer, functional annotation enrichment analysis indicated its co-expressed genes were enriched in certain pathways, and miR-485-5p negatively regulates its expression [5]. In colorectal adenocarcinoma, knockdown of Ppfia4 affected cell stemness, proliferation, migration and apoptosis [6]. In vitro studies also showed that knockdown of Ppfia4 inhibited the proliferation and migration promoting effect in colon adenocarcinoma cells [7].

In conclusion, Ppfia4 plays a significant role in promoting cancer-related processes such as metabolism, proliferation, migration and invasion in various cancer types including prostate, esophageal, colon, ovarian and colorectal cancers. These findings from gene-based functional studies, especially loss-of-function experiments in cell lines and mouse models, provide insights into its functions and potential as a therapeutic target in cancer.