Nod1, a member of the nucleotide-binding oligomerization domain (NOD) proteins and an intracellular NOD-like receptor, senses conserved motifs in bacterial peptidoglycan. It induces pro-inflammatory and antimicrobial responses by activating downstream signaling pathways such as NF-κB and mitogen-activated protein kinase (MAPK) through engaging the adaptor protein RIP2. Nod1 is crucial for host immune response, and its function is also associated with various biological processes and diseases [1,2,3].

In a genetic and chemical embryonic model, HSPCs failed to specify in the absence of Nod1 and its downstream kinase Ripk2 due to a failure in hemogenic endothelial (HE) programming, indicating that Nod1-dependent NF-κB activation is essential for hematopoietic stem cell specification in response to small Rho GTPases [4]. NOD1-deficient models are protected from high-fat diet (HFD)-induced insulin resistance, and hematopoietic NOD1 deficiency prevented HFD-induced changes in pro-inflammatory macrophage polarization status, suggesting Nod1 contributes to the development of insulin resistance [6]. In breast cancer, enterotoxigenic Bacteroides fragilis-secreted BFT-1 promotes breast cancer cell stemness and chemoresistance by directly binding to NOD1, and NOD1 inhibition increases chemosensitivity [5].

In conclusion, Nod1 plays a vital role in host immune response, hematopoietic stem cell specification, insulin resistance, and breast cancer chemoresistance. Studies using gene knockout models, such as Nod1-deficient models, have significantly contributed to understanding its function in these biological processes and disease conditions, providing insights into potential therapeutic strategies for related diseases.