RIMBP2 (RIMS binding protein 2) functions as a presynaptic bifunctional linker protein that simultaneously interacts with RIMS1, RIMS2, and voltage-gated calcium channels (CACNA1D and CACNA1B) to regulate synaptic transmission 12. The protein is critical for normal neuromuscular synaptic function and plays an essential role in synaptic development and plasticity in cortical neurons. RIMBP2 dysregulation has significant disease relevance across multiple conditions. In Pitt-Hopkins syndrome (PTHS), caused by TCF4 mutations, RIMBP2 emerges as the most differentially expressed gene in patient-derived neurons, with reduced expression contributing to deficits in spontaneous synaptic transmission, network excitability, and homeostatic plasticity 12. Remarkably, restoring RIMBP2 expression rescues these synaptic deficits, identifying it as a critical therapeutic target. RIMBP2 dysfunction has also been associated with anxiety disorders, as altered DNA methylation at RIMBP2 loci correlates with anxiety disorder status independent of depression comorbidity 3. Additionally, RIMBP2 shows potential clinical relevance in hearing function and appears implicated in various cancers and pulmonary disease susceptibility based on genetic studies 45. These findings position RIMBP2 as a crucial regulator of presynaptic function with broad implications for neuropsychiatric and developmental disorders.