NRBP1 (nuclear receptor binding protein 1) is a pseudokinase with diverse cellular functions spanning ion homeostasis, neuropsychiatric signaling, and retrotransposon regulation. Primary Function: NRBP1 serves as an upstream activator of the WNK kinase pathway, which regulates osmotic stress responses and epithelial ion transport 1. In the kidney's distal convoluted tubule, NRBP1 acts as a positive modulator of WNK signaling, affecting NaCl cotransporter phosphorylation and sodium reabsorption 2. Mechanism: NRBP1 functions through protein-protein interactions, forming complexes with WNK isoforms and TSC22D adaptor proteins via its conserved C-terminal domain 1. In microglia, (R)-ketamine activates an ERK-NRBP1-CREB-BDNF signaling cascade that produces sustained antidepressant effects 3. NRBP1 also regulates long interspersed nuclear element-1 (L1) retrotransposition by influencing L1 ribonucleoprotein complex integrity, with its paralog NRBP2 antagonistically regulating this function through NRBP1 degradation 4. Disease Relevance: Genetic variants in NRBP1 associate with alcohol use disorder and problem drinking 5, functional outcome after ischemic stroke 6, and gastric cancer progression where TRIM24-mediated NRBP1 degradation promotes tumor metastasis 7. Clinical Significance: NRBP1 represents a therapeutic target for treating depression, stroke outcomes, and gastric cancer, with mechanistic insights enabling potential intervention strategies.