Btnl9, or butyrophilin-like protein 9, is a member of the immunoglobulin families. It appears to be involved in immune-related and cancer-related pathways [1]. However, its exact function and associated molecular mechanisms are still being explored, and genetic models such as knockout (KO) mouse models could potentially provide more insights into its essential functions.

In various cancers, Btnl9 shows significant associations. In thyroid cancer, its expression is down-regulated, and lower expression is associated with a poorer progression-free interval. Gene enhancers of Btnl9 have different H3K27ac modifications in papillary thyroid cancer and benign thyroid nodule tissues [1].

In breast cancer, its expression is declined, and ectopic expression inhibits cell proliferation, colony formation, and metastasis, while knockdown has the opposite effect. It blocks breast cancer cells in the G2/M phase via the P53/CDC25C and P53/GADD45 pathways [2].

In non-small-cell lung cancer, lncRNA CALML3-AS1 inhibits Btnl9 transcription and expression through the recruitment of Zeste homolog 2 (EZH2), and Btnl9 down-regulation counteracts the antitumor effects of sh-CALML3-AS1 [3].

In uveal melanoma, Btnl9 mRNA levels are lower in tumor tissues, and high expression is associated with a favorable prognosis. It can suppress invasion in melanoma cell lines [4].

In lung adenocarcinoma, Btnl9 expression is down-regulated and associated with a poor probability of overall survival, and it is positively correlated with immune cell infiltration levels [5].

In pancreatic cancer, decreased expression of Btnl9 is associated with a reduced survival rate [6].

In BRAF-mutated peritoneal metastasis from colorectal cancer, there is increased expression of Btnl9 [7].

In idiopathic pulmonary fibrosis, Btnl9 is down-regulated in patient tissues and Bleomycin-induced mice, and it may have a protective effect by inhibiting extracellular matrix production and promoting wound repair [8].

In amyotrophic lateral sclerosis, a Mendelian randomization study shows a negative correlation between Btnl9 and the disease [9].

In conclusion, Btnl9 is involved in multiple biological processes, especially in relation to cancer progression and immune-related functions. The findings from various disease-related studies, although not from KO/CKO mouse models in the provided references, suggest its potential as a prognostic biomarker and a possible therapeutic target in different cancers and other diseases.