CARS1, cysteinyl-tRNA synthetase 1, is an enzyme that attaches cysteine to its cognate tRNA, playing a crucial role in protein synthesis. It is also associated with ferroptosis-a non-apoptotic form of cell death, and may be involved in immune-related pathways [4,5,7,8,9]. Genetic models, such as gene knockout or knockdown, could potentially be used to study its functions in more detail.

Autoantibodies to cytoplasmic CARS1 were identified as a new antisynthetase autoantibody (ASA) specificity, named anti-Ly, in a patient with antisynthetase syndrome (ASyS) features [1]. A patient with a CARS1-ALK fusion in metastatic inflammatory myofibroblastic tumor (IMT) showed significant tumor regression with alectinib targeted therapy [2]. Loss-of-function CARS1 variants in a patient led to a multisystem disease including microcephaly, developmental delay, and brittle hair and nail phenotypes [3]. In esophageal squamous cell carcinoma (ESCC), CARS1 promoted ferroptosis-induced cell death by regulating GPX4 expression [4]. In mesothelioma, high CARS1 expression was associated with an unfavorable prognosis, and it was part of a ferroptosis-related prognostic gene signature [5]. CARS1 could be secreted from cancer cells to activate immune responses via TLR2/6, and a domain within it showed potential as an immunoadjuvant [6]. CARS1 was also involved in a ferroptosis-related prognosis model in colon cancer, esophageal adenocarcinoma, and clear cell renal cell carcinoma [7,8,9].

In conclusion, CARS1 is essential for protein synthesis and has significant implications in multiple disease conditions, including autoimmunity, cancer, and multisystem disorders. Functional studies using gene knockout or knockdown models, as indicated by the research, could further clarify its role in these biological processes and diseases, potentially providing new therapeutic targets.