TRPC4AP is a substrate-recognition component of a DCX (DDB1-CUL4) E3 ubiquitin-protein ligase complex essential for cell cycle control 1. It specifically mediates polyubiquitination and degradation of MYC through the DesCEND (C-end degron) pathway, recognizing proteins with an arginine at the minus-3 position at their C-terminus 12. TRPC4AP also functions in calcium signaling, with recent evidence demonstrating that it partners with TRPC4 to enable hydrogen gas-triggered, reversible calcium transients via plasma membrane Ca²⁺ influx, with a critical dual-arginine motif in TRPC4 mediating this interaction 3. Disease relevance is substantial across multiple conditions. Rare coding variants in TRPC4AP associate with neuroticism in large exome studies 4, and common variants show convergent evidence for this association 4. A TRPC4AP haplotype is enriched in late-onset Alzheimer's disease patients (36% vs. 26% in controls; OR=1.56) 56, potentially linked to behavioral changes and hallucinations. Transcriptome-wide association identifies TRPC4AP/NCOA6 in restless legs syndrome susceptibility 7. Mendelian randomization analysis suggests TRPC4AP as a potential therapeutic target for coronary heart disease 8. These findings establish TRPC4AP as a multifunctional protein relevant to neurological and cardiovascular disease pathogenesis.