SPINK5, also known as serine peptidase inhibitor Kazal-type 5, is involved in multiple biological processes. It has been linked to immune-related pathways, especially the TLR4/NF-κB pathway, and is important for maintaining normal cellular functions in various tissues [1].

SPINK5 mRNA levels are downregulated in several cancers. In esophageal squamous cell carcinoma (ESCC), lower SPINK5 mRNA levels are associated with higher lymph node metastases, and overexpressed SPINK5 inhibits cell invasion and migration. It is also negatively correlated with NF-κB signaling pathway-related genes, and its regulation affects NF-κB promoter activity. Additionally, it is significantly correlated with immune cells infiltration [1]. In non-small cell lung carcinoma, SPINK5 is lowly expressed, predicts tumor staging and lymphatic metastasis, and acts as a tumor-suppressor gene by negatively regulating PSIP1 [2]. In laryngeal squamous cell carcinoma, SPINK5 is identified as a potential prognostic biomarker, and its downregulation may promote tumorigenesis through the "BASAL CELL CARCINOMA" pathway and disrupt DNA damage and repair pathways [4]. Netherton syndrome, a rare autosomal recessive genodermatosis, is caused by pathogenic variants in the SPINK5 gene [3,5,6].

In conclusion, SPINK5 plays crucial roles in tumor metastasis, immune-related processes, and skin-related genetic diseases. Studies on SPINK5 in various disease models, especially in cancer, help to understand its functions in disease occurrence and progression, providing potential biomarker and therapeutic targets for related diseases.