Updated project metadata. Background: Inherited Platelet Disorders (IPDs) are a heterogeneous group of rare diseases that are caused by defects in early megakaryopoiesis, pro-platelet formation and/or mature platelet function. Although genomic sequencing is increasingly used to identify genetic variants underlying IPD, this technique does not disclose resulting molecular changes that impact platelet function. Proteins are the functional units that shape platelet function, however insights into how variants that cause IPDs impact platelet proteomes is limited. Objectives: To profile the platelet proteomics signatures of inherited platelet disorders. Methods: We performed unbiased label free quantitative mass spectrometry (MS)-based proteome profiling on platelets of 34 IPD patients with variants in 13 ISTH TIER1 genes that affect different stages of platelet development. Results: In line with the phenotypical heterogeneity between IPDs, proteomes were diverse between IPDs. We observed extensive proteomic alterations in patients with a GFI1B variant and for genetic variants in genes encoding proteins that impact cytoskeletal processes (MYH9, TUBB1 and WAS). Utilizing the diversity between IPDs, we clustered protein dynamics, revealing disrupted protein-protein-complexes. This analysis furthermore grouped proteins with similar cellular- function and location, classifying mitochondrial protein constituents and identifying both known and putative novel alpha granule associated proteins. Conclusions: With this study we demonstrate a MS-based proteomics perspective to IPDs. By integrating the effects of IPDs that impact different aspects of platelet function, we dissected the biological contexts of protein alterations to gain further insights into the biology of platelet (dys)function.