GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE304nnn/GSE304289/primary200OKTranscriptomicsMus musculusExpression profiling by arrayhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE304289GEOGSEfalseCaspase-3 Control of RNA Splicing and Mitochondrial Dynamics in Microglia during Parkinson’s DiseaseCaspase-3, a cysteine-aspartic protease canonically known for its role in apoptotic cell death, has been implicated in several non-apoptotic functions, particularly in microglia, the brain-resident macrophages. These novel functions appear to depend on distinct levels of caspase-3 activation; however, the role of basal caspase-3 activity remains unclear. Here, we show that basal caspase-3 regulates RNA splicing in microglia, and its inhibition in a Parkinson´s disease (PD) model leads to splicing dysregulation. Loss of basal caspase-3 activity also increases double-stranded RNA (dsRNA) accumulation, inducing a type I interferon response. Additionally, caspase-3 deficiency impairs mitochondrial respiration, reduces ATP production, and causes sex-specific mitochondrial abnormalities, predominantly in female microglia. Together, our findings uncover a non-apoptotic, homeostatic role for basal caspase-3 activity in microglia. Its disruption, such as in PD, may drive key molecular features of neuroinflammation and neurodegeneration, positioning caspase-3 as a critical regulator of microglial function in health and disease.2026/08/06GSE304289GSM9146835GSM9146824GSM9146823GSM9146834GSM9146833GSM9146822GSM9146832GSM9146821GSM9146820GSM9146831GSM9146830GSM9146819GSM9146818GSM9146829GSM9146828GSM9146817GSM9146838GSM9146827GSM9146816GSM9146815GSM9146826GSM9146837GSM9146836GSM914682523038304289Mus musculus