Platelet α-granules are essential for normal platelet function and play a crucial role in various physiological and pathological processes. These granules, derived from megakaryocytes, contain a diverse array of bioactive proteins that are released upon platelet activation. The formation of α-granules involves both regulated secretory and endocytic pathways, with SNARE proteins and their accessory proteins mediating the release of granule contents. α-Granules fuse with the plasma membrane, increasing platelet surface area and releasing their cargo. Proteomic studies have identified hundreds of proteins in α-granules, including adhesion molecules, chemokines, growth factors, and antimicrobial peptides. These proteins contribute to thrombosis, hemostasis, inflammation, atherosclerosis, antimicrobial defense, wound healing, angiogenesis, and malignancy. Defects in α-granule formation, such as those seen in Gray Platelet Syndrome, can lead to bleeding disorders. The release of α-granules is regulated by SNARE proteins, SM proteins, and other factors, ensuring precise and controlled secretion. α-Granules contain both pro- and anti-angiogenic factors, which may contribute to their role in angiogenesis and tumor progression. Understanding the detailed mechanisms of α-granule formation, release, and function is crucial for developing therapeutic strategies targeting platelet α-granules in various diseases.Platelet α-granules are essential for normal platelet function and play a crucial role in various physiological and pathological processes. These granules, derived from megakaryocytes, contain a diverse array of bioactive proteins that are released upon platelet activation. The formation of α-granules involves both regulated secretory and endocytic pathways, with SNARE proteins and their accessory proteins mediating the release of granule contents. α-Granules fuse with the plasma membrane, increasing platelet surface area and releasing their cargo. Proteomic studies have identified hundreds of proteins in α-granules, including adhesion molecules, chemokines, growth factors, and antimicrobial peptides. These proteins contribute to thrombosis, hemostasis, inflammation, atherosclerosis, antimicrobial defense, wound healing, angiogenesis, and malignancy. Defects in α-granule formation, such as those seen in Gray Platelet Syndrome, can lead to bleeding disorders. The release of α-granules is regulated by SNARE proteins, SM proteins, and other factors, ensuring precise and controlled secretion. α-Granules contain both pro- and anti-angiogenic factors, which may contribute to their role in angiogenesis and tumor progression. Understanding the detailed mechanisms of α-granule formation, release, and function is crucial for developing therapeutic strategies targeting platelet α-granules in various diseases.