SRRM2 (serine/arginine repetitive matrix 2) is a nuclear splicing factor that serves as an essential scaffold protein for nuclear speckle organization and RNA processing. SRRM2 forms biomolecular condensates through liquid-liquid phase separation and, together with SON, constitutes the core structural component of nuclear speckles, with co-depletion of both proteins leading to near-complete dissolution of these nuclear organelles 1. The protein regulates alternative splicing by promoting interactions between mRNA and spliceosome machinery, particularly affecting cassette exons with short introns and weak splice sites 2. SRRM2's splicing activity is modulated by extensive phosphorylation within its intrinsically disordered region by casein kinase 2, which enhances nuclear speckle relaxation and mRNA splicing efficiency during DNA damage responses 3. Loss-of-function variants in SRRM2 cause intellectual developmental disorder, autosomal dominant 72, characterized by mild developmental delay, speech delays, autism spectrum features, hypotonia, and dysmorphic facial features in 22 reported patients 4. SRRM2 dysfunction is also implicated in neurodegenerative diseases, as the protein mislocalizes to cytoplasmic tau aggregates in Alzheimer's disease and frontotemporal dementia, contributing to altered nuclear speckle dynamics and aberrant splicing 5. Additionally, SRRM2 is critical for maintaining embryonic stem cell pluripotency and proper cell fate decisions during early development 6.