**Background:** Platelets, traditionally known for their roles in hemostasis and coagulation, are the most prevalent blood component after erythrocytes (150,000–400,000 platelets/μL in healthy humans). However, only 10,000 platelets/μL are needed for vessel wall repair and wound healing. Increased knowledge of the platelet's role in hemostasis has led to many advances in understanding that they are crucial mediators in many other physiological processes, such as innate and adaptive immunity. Due to their multiple functions, platelet dysfunction is involved not only in thrombosis, mediating myocardial infarction, stroke, and venous thromboembolism, but also in several other disorders, such as tumors, autoimmune diseases, and neurodegenerative diseases. On the other hand, thanks to their multiple functions, nowadays platelets are therapeutic targets in different pathologies, in addition to atherothrombotic diseases; they can be used as an innovative drug delivery system, and their derivatives, such as platelet lysates and platelet extracellular vesicles (pEVs), can be useful in regenerative medicine and many other fields. The protean role of platelets, from the name of Proteus, a Greek mythological divinity who could take on different shapes or aspects, is precisely the focus of this review.
**Methods:** This is a narrative review that synthesizes existing literature on platelet biology, platelet derivatives, and their clinical applications. The authors discuss platelet granules and receptors, platelet concentrates (PCs) and their medical applications, platelet roles in disease (atherosclerosis, cancer, neurodegenerative conditions), platelet extracellular vesicles (pEVs), and platelets as drug delivery vehicles. The review includes a search on clinicaltrials.gov using keywords such as "platelet gel", "platelet lysate", "platelet derivatives", "platelet-rich plasma", "platelet-rich fibrin", "serum eyedrop", and "platelet-rich plasma eyedrop", identifying 920 interventional and 41 observational studies, mostly in orthopedics, dentistry, and maxillofacial surgery.
**Key Results:** Platelets contain α-granules and dense granules (δ granules) that release over 300 soluble proteins, including coagulation factors, chemotactic factors (e.g., PF4, β-thromboglobulin, RANTES, MCP-1, MIP-1α), and immunomodulatory molecules (e.g., CD40L, TGF-β1). Platelet concentrates (PCs) have been classified into pure platelet-rich plasma (P-PRP), leukocyte and platelet-rich plasma (L-PRP), pure platelet-rich fibrin (P-PRF), leukocyte and platelet-rich fibrin (L-PRF), platelet gel (PG), platelet lysate (PL), serum eye drops (E-S), and PRP eye drops (E-PRP). PCs have been used in wound healing, bone repair, osteoarthritis, dry eye syndrome, corneal ulcers, and macular holes. Platelets are involved in atherosclerosis through P-selectin-mediated adhesion and leukocyte recruitment, and in cancer through tumor-induced platelet aggregation, metastasis protection, and angiogenesis. In neurodegenerative diseases, platelets promote neurogenesis via growth factors (VEGF, EGF, FGF-2, IGF-1, PF4, TGF-β, SDF-1) and neurotransmitters (serotonin, histamine, epinephrine, dopamine). Platelet extracellular vesicles (pEVs) are produced from platelets and contain growth factors, cytokines, chemokines, lipids, neurotransmitters, and nucleic acids. pEVs have been shown to promote fibroblast and keratinocyte migration, enhance stem cell engraftment, and have angiogenic potential. Platelets can also be used as drug delivery vehicles, exploiting their ability to encapsulate drugs and release them upon activation.
**Clinical Implications:** Antiplatelet drugs (e.g., aspirin, clopidogrel) are first-choice therapy for cardiovascular disease and show potential in cancer and neurodegenerative disease treatment. Platelet derivatives, particularly PRP and pEVs, offer therapeutic options in regenerative medicine, wound healing, orthopedics, ophthalmology, and neurology. pEVs can cross the blood-brain barrier, making them promising for central nervous system disorders. Platelets as drug delivery vehicles could provide targeted therapy with reduced systemic effects, especially in oncology and stroke. However, standardization of preparation protocols and further clinical studies are needed to fully realize their potential.