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Amyloid\u2010related disorders are the most common proteinopathies and are characterized by amyloid fibril deposits in the brain or other organs. Aging is generally associated with the development of these amyloid\u2010related disorders, but we still do not fully understand how functional proteins become pathogenic amyloid deposits during the human aging process. We identified a novel amyloidogenic protein, named epidermal growth factor\u2010containing fibulin\u2010like extracellular matrix protein 1 (EFEMP1), in massive venous amyloid deposits in specimens that we obtained from an autopsied patient who died of gastrointestinal bleeding. Our postmortem analyses of additional patients indicate that EFEMP1 amyloid deposits frequently developed in systemic venous walls of elderly people. EFEMP1 was highly expressed in veins, and aging enhanced venous EFEMP1 expression. In addition, biochemical analyses indicated that these venous amyloid deposits consisted of C\u2010terminal regions of EFEMP1. <jats:italic>In vitro<\/jats:italic> studies showed that C\u2010terminal regions formed amyloid fibrils, which inhibited venous tube formation and cell viability. EFEMP1 thus caused a novel age\u2010related venous amyloid\u2010related disorder frequently found in the elderly population. Understanding EFEMP1 amyloid formation provides new insights into amyloid\u2010related disorders occurring during the aging process. Copyright \u00a9 2018 Pathological Society of Great Britain and Ireland. 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