Cerebral cavernous malformation (CCM) is a common vascular disease in central 
nervous system that frequently predisposes to stroke, seizure, and cerebral 
hemorrhage. CCM lesions are characterized by dilated and leaky intracranial 
capillaries composed of a thin layer of vascular endothelial cells with abnormal 
subendothelial extracellular matrix. Despite the understanding that genetic 
mutation of three CCM genes (CCM1, CCM2, and CCM3) results in hereditary CCM, 
the molecular mechanism underlying vascular defects in CCM lesions remains 
poorly understood. Recent studies have shown that integrin cytoplasmic 
domain-associated protein-1 (ICAP-1, also known as integrin β1 binding protein1, 
ITGB1BP), a cytoplasmic protein interacting with both β1 integrin subunit and 
CCM1 protein (also known as Krit1), is implicated in vascular development. 
Analysis of data on the biochemistry and cellular biology of ICAP-1 highlights 
that bidirectional interaction of ICAP-1 with CCM1 and integrin might regulate 
diverse pathological processes of CCM disorder. Specifically, emerging evidence 
supports the hypothesized involvement of ICAP-1 in CCM pathogenesis through its 
significant effect in attenuating excessive vascular growth, its indispensable 
function in activating CCM1 protein, and its essential role in regulating 
integrin functions.