Endothelial cell-specific membrane protein involved in the formation of the diaphragms that bridge endothelial fenestrae. It is also required for the formation of stomata of caveolae and transendothelial channels. Functions in microvascular permeability, endothelial fenestrae contributing to the passage of water and solutes and regulating transcellular versus paracellular flow in different organs. Plays a specific role in embryonic development. Homodimer. Membrane-associated protein of caveolae. Found in fenestral and stomatal diaphragms in fenestrated endothelia and transendothelial channels. Also colocalized with CAV1 in perinuclear region. Expressed in lung, kidney, spleen, heart, muscle, eye, pancreas, thyroid, thymus, submaxillary gland, prostate, epididymis, uterus and liver. Expressed in embryo at 7 dpc. Expressed in the brain vasculature at 12 up to 16 dpc, whereupon it disappears. Mutant animals result in lethality during prenatal development. Examination of the homozygous deficient embryos reveal subcutaneous edema, hemorrhages and defects in the vascular wall of subcutaneous capillaries. Hearts of deficient embryos show ventricular septal defects (VSDs) and thinner ventricular walls, as well as blood abnormalities. Analyses on protein expression and localization in endothelial cells of subcutaneous capillaries and endocardium show that the protein and caveolae with stomatal diaphragm were present in wild-type embryos, whereas the diaphragm is missing in the caveolae of deficient embryos. Deficient mice are viable after birth and survive up to 4 weeks on a mixed C57BL/6N/FVB-N background. Embryos on the mixed background show edema in neck and back, but no visible hemorrhages. Postnatal mutant mice display marked reduction in body size and kinked tails compare with wild-type, but no VSDs are observed in hearts. Detailed examination of the capillaries of kidneys and pancreas reveal that the knockout mice does not form fenestrae with diaphragm.