A comprehensive classification of proteoglycan gene families and their respective protein cores is presented, based on three criteria: cellular and subcellular location, overall gene/protein homology, and the presence of specific protein modules within their cores. Proteoglycans are divided into four major classes: intracellular, cell-surface, pericellular, and extracellular. These classes include 43 distinct proteoglycan-encoding genes and numerous alternatively spliced variants. The biological functions of these proteoglycans are discussed in development, cancer, angiogenesis, and various diseases. Intracellular proteoglycans include serglycin, the only proteoglycan with heparin side chains, which is stored in mast cell granules and modulates protease activity. Cell-surface proteoglycans include syndecans, CSPG4/NG2, betaglycan, phosphacan, and glypicans. Syndecans are transmembrane proteoglycans that interact with various ligands and growth factors, and their shedding can influence angiogenesis and cancer progression. CSPG4/NG2 is a transmembrane proteoglycan involved in tumor vascularization and can modulate FGF availability. Betaglycan acts as a co-receptor for TGFβ superfamily members and can suppress tumor growth. Phosphacan interacts with neurons and N-CAM, and is involved in neural development. Glypicans are GPI-anchored proteoglycans that modulate signaling pathways and are involved in tumor growth and angiogenesis. Pericellular and basement membrane proteoglycans include perlecan, agrin, collagens XVIII and XV. Perlecan is a large HSPG involved in various biological processes, including angiogenesis and tissue development. Agrin is involved in neuromuscular junction formation and can modulate neuronal outgrowth. Collagens XVIII and XV are involved in vascular and basement membrane formation and have anti-angiogenic properties. Extracellular proteoglycans include hyalectans, which bind hyaluronan and form supramolecular complexes. Aggrecan is a major proteoglycan in cartilage, forming large aggregates that provide structural support. Other proteoglycans, such as versican, neurocan, and brevican, have diverse functions in development and disease. The study highlights the importance of proteoglycans in various biological processes and their potential as therapeutic targets.A comprehensive classification of proteoglycan gene families and their respective protein cores is presented, based on three criteria: cellular and subcellular location, overall gene/protein homology, and the presence of specific protein modules within their cores. Proteoglycans are divided into four major classes: intracellular, cell-surface, pericellular, and extracellular. These classes include 43 distinct proteoglycan-encoding genes and numerous alternatively spliced variants. The biological functions of these proteoglycans are discussed in development, cancer, angiogenesis, and various diseases. Intracellular proteoglycans include serglycin, the only proteoglycan with heparin side chains, which is stored in mast cell granules and modulates protease activity. Cell-surface proteoglycans include syndecans, CSPG4/NG2, betaglycan, phosphacan, and glypicans. Syndecans are transmembrane proteoglycans that interact with various ligands and growth factors, and their shedding can influence angiogenesis and cancer progression. CSPG4/NG2 is a transmembrane proteoglycan involved in tumor vascularization and can modulate FGF availability. Betaglycan acts as a co-receptor for TGFβ superfamily members and can suppress tumor growth. Phosphacan interacts with neurons and N-CAM, and is involved in neural development. Glypicans are GPI-anchored proteoglycans that modulate signaling pathways and are involved in tumor growth and angiogenesis. Pericellular and basement membrane proteoglycans include perlecan, agrin, collagens XVIII and XV. Perlecan is a large HSPG involved in various biological processes, including angiogenesis and tissue development. Agrin is involved in neuromuscular junction formation and can modulate neuronal outgrowth. Collagens XVIII and XV are involved in vascular and basement membrane formation and have anti-angiogenic properties. Extracellular proteoglycans include hyalectans, which bind hyaluronan and form supramolecular complexes. Aggrecan is a major proteoglycan in cartilage, forming large aggregates that provide structural support. Other proteoglycans, such as versican, neurocan, and brevican, have diverse functions in development and disease. The study highlights the importance of proteoglycans in various biological processes and their potential as therapeutic targets.