Nrip2, or Nuclear Receptor-Interacting Protein 2, is involved in modulating the Wnt pathway. It has been shown to play a role in the self-renewal of colorectal cancer initiating cells (CCICs) by interacting with components of the Wnt pathway, and is also associated with other biological processes such as granulosa cell function regulation by FSH [1,2].

In CCICs, NRIP2 was significantly up-regulated. Overexpression of NRIP2 increased Wnt activity, while its silencing attenuated Wnt activity. NRIP2 regulated Wnt pathway activity through targeting the transcription factor RORβ, which is a transcriptional enhancer of the Wnt pathway inhibitor HBP1. NRIP2 prevented RORβ from binding to the HBP1 promoter regions, reducing HBP1 transcription and thus attenuating HBP1-dependent inhibition of TCF4-mediated transcription [1]. In podocyte injury, NRIP2 knockdown accelerated β-catenin degradation, while overexpression led to β-catenin activation. Genetic knockout of Nrip2 in adriamycin-induced nephropathy mice ameliorated podocyte injury, glomerulosclerosis, and proteinuria by inhibiting β-catenin activation. NRIP2 was also upregulated in podocytes of patients with focal segmental glomerulosclerosis (FSGS) [3].

In conclusion, NRIP2 plays important roles in modulating the Wnt pathway in colorectal cancer-related cell self-renewal and in podocyte injury through its interaction with β-catenin. The study of Nrip2 knockout mouse models has provided insights into its function in these disease-related processes, contributing to our understanding of the underlying molecular mechanisms in colorectal cancer and podocyte-related kidney diseases.