MAEL, also known as maelstrom spermatogenic transposon silencer, is a cancer-testis antigen-associated gene. It is essential for mammalian meiotic progression and post-meiotic spermiogenesis, as it induces transposon repression in the male germline [8]. In addition, MAEL is involved in metabolic reprogramming, stemness regulation, and cancer progression, and may be related to drug resistance and serve as a diagnostic marker in some cancers [2,3,4,7,9].

In human spermatozoa, MAEL is prominently expressed in the mitochondria of ejaculated spermatozoa. Knockdown of MAEL in human H358 cells sabotages mitochondria function and reduces ATP production, and its decreased expression is associated with asthenozoospermia [1]. In breast cancer, MAEL promotes a metabolic shift from oxidative phosphorylation to glycolysis by inducing chaperone-mediated autophagy-dependent degradation of citrate synthase and fumarate hydratase, thus promoting cancer progression [2]. In hepatocellular carcinoma, MAEL augments cancer stemness properties and resistance to sorafenib through the PTGS2/AKT/STAT3 axis [3]. In esophageal squamous cell carcinoma, MAEL is mainly involved in primary stages of tumor progression and can be an early-detection marker [4]. In clear cell renal cell carcinoma, MAEL expression is associated with prognosis, the tumor immune microenvironment, and response to VEGFR/mTOR inhibitors and immunotherapy [5]. In gastric cancer, MAEL promotes the lysosome-dependent degradation of ILKAP, contributing to cancer progression [6]. In T-cell acute lymphoblastic leukemia, MAEL promotes drug resistance by increasing the expression of MRP and LRP genes [7]. In human hypospermatogenesis, hypermethylation of the MAEL promoter is associated with de-repression of LINE-1 [8].

In conclusion, MAEL plays crucial roles in spermatogenesis, metabolism, cancer stemness, and cancer progression. Studies on MAEL gene knockout or knockdown models in various cell lines and in vivo models have revealed its functions in different biological processes and disease conditions, such as male infertility and multiple cancers. These findings provide important insights into understanding the molecular mechanisms underlying these processes and may offer potential targets for disease diagnosis and treatment.