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Many secreted polypeptide regulators of angiogenesis are devoid of signal peptides. These proteins are released through nonclassical pathways independent of endoplasmic reticulum and Golgi. In most cases, the nonclassical protein export is induced by stress. It usually serves to stimulate repair or inflammation in damaged tissues. We review the secreted signal peptide-less regulators of angiogenesis and discuss the mechanisms and biological significance of their unconventional export.