Il1rapl2, Interleukin 1 Receptor Accessory Protein-Like-2, is a gene mapping to Xq22. It shares domains, exon-intron organization, and high protein-level similarity (70.4%) with IL1RAPL1, a gene related to X-linked mental retardation [1]. Il1rapl2 is specifically expressed in the central nervous system from embryonic day 12.5, suggesting its importance in CNS-related functions [1].

In a study on cortical aging, Il1rapl2 was identified as one of the differential genes/proteins whose expression trend was correlated with brain aging, indicating its potential as a biomarker for brain aging [2]. In esophagus squamous cell carcinoma (ESCC), Il1rapl2 was among the tumor-grade-related mRNAs, with its alterations potentially providing insights into the molecular mechanisms of ESCC [3]. In autism spectrum disorders (ASD), Il1rapl2 was one of the candidate genes analyzed in a region on the X-chromosome, where its mutation screening was carried out [4]. In head and neck squamous cell carcinoma (HNSCC), Il1rapl2 was poorly expressed and was a prognostic risk factor, affecting the microenvironment changes and survival prognosis of HNSCC patients [5]. A recent study also found that Il1rapl2-expressing neurons in the medial prefrontal cortex (mPFC) are involved in regulating social novelty preference [6].

In conclusion, Il1rapl2 is mainly expressed in the central nervous system and is associated with various neurological and cancer-related conditions. Its role as a biomarker in brain aging, its relation to tumor-grade in ESCC, and its potential association with ASD highlight its significance in understanding these disease mechanisms. The identification of its role in regulating social novelty preference further expands our knowledge of its functions in social behavior-related neural circuits.