Netrin-Like Protein (NLP)

The target name "Nezha/NLP protein" is ambiguous and appears to conflate two distinct biological proteins. "Nezha" is an alias for Calmodulin-regulated spectrin-associated protein 3 (CAMSAP3), a microtubule-associated protein involved in organizing non-centrosomal microtubules. The "NLP protein" refers to Netrin-Like Protein, also known as C17ORF58. This response focuses on Netrin-Like Protein (NLP) as it has been explicitly identified as a promising therapeutic target. Netrin-Like Protein (NLP), encoded by the C17ORF58 gene, is a novel regulator of the G2-M phase of the cell cycle. It is critical for the proliferation of malignant T-cells, and its depletion leads to G2-M arrest and mitotic catastrophe, culminating in apoptosis in cancer cells. NLP is significantly overexpressed in over 95% of Peripheral T-cell lymphoma (PTCL) cases, including Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, and PTCL-Not Otherwise Specified, as well as in various solid tumors such as breast, renal, and liver cancers. Its predicted druggable structure makes it a promising candidate for the development of novel targeted therapies for PTCL. Notably, NLP depletion does not affect the proliferation of normal human T-cells or other normal cell types, and homozygous knockout mice are viable, suggesting a potentially favorable therapeutic window for drugs targeting this protein.

Other names

C17ORF58

Induces G2-M arrest and mitotic catastrophe, leading to apoptosis in malignant T-cells.