COL4A2 encodes the α2 chain of type IV collagen, which forms heterotrimers with two α1 chains (COL4A1) as essential components of basement membranes across multiple tissues 1. These collagen IV networks provide structural integrity and contribute to cell regulation in vascular, renal, and other organ systems 2. Pathogenic variants in COL4A2 cause autosomal dominant multisystem disorders with highly variable penetrance and expressivity 3. The neurological manifestations are most prominent, including porencephaly, intracerebral hemorrhage, stroke, seizures, and intellectual disability 14. COL4A2 variants are associated with cerebral small vessel disease, with genome-wide association studies identifying COL4A2 as a risk locus for lacunar stroke 5. The protein's cleavage product canstatin possesses anti-angiogenic properties through integrin binding and apoptosis induction. Beyond neurological disease, COL4A2 variants cause ophthalmological abnormalities including retinal vascular tortuosity and cataracts, as well as renal manifestations such as hematuria 3. Fetal intracranial hemorrhage represents another important clinical presentation, with COL4A2 variants identified in 19% of affected fetuses 6. Management requires multidisciplinary surveillance given the multiorgan involvement and unpredictable disease progression.