JAML, also known as junctional adhesion molecule-like protein, is involved in multiple biological processes. It serves as a co-stimulatory molecule in γδ T cells [4,6]. In T cells, its interactions with ligand coxsackie and adenovirus receptor (CXADR) support antitumor immunity of CD8 and γδ T cells, indicating its importance in cancer immunotherapy [6]. It is also related to the regulation of immune cell migration [8].

In mouse models, podocyte-specific deletion of Jaml ameliorated podocyte injury and proteinuria in diabetic mice, suggesting its role in promoting diabetic kidney disease through modulating podocyte lipid metabolism via SIRT1-mediated SREBP1 signaling [1]. In acute kidney injury murine models, JAML was significantly upregulated, and macrophage-specific and tubular cell-specific Jaml conditional knockout mice demonstrated that JAML promoted AKI mainly via a macrophage-dependent mechanism [2]. In colorectal cancer, overexpression of JAML promoted tumor proliferation by activating the PI3K-AKT-mTOR signalling pathway, while in another study, decreased JAML expression in colon cancer tissues was observed and overexpression of JAML could promote T cell proliferation and down-regulate immune checkpoints [3,7]. In lung cancer, JAML promoted the antitumor role of tumor-resident CD8+ T cells by facilitating their innate-like function [5].

In conclusion, JAML plays diverse and crucial roles in various biological processes and diseases. Gene knockout and conditional knockout mouse models have been instrumental in revealing its functions in diseases such as diabetic kidney disease, acute kidney injury, and cancers like colorectal and lung cancer. These studies suggest JAML could be a potential therapeutic target for these diseases.