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The Factor H protein family: The switchers of the complement alternative pathway


Dive into the intricate world of the Factor H (FH) protein family with LAURA LUCIENTES CONTINENTE, Bárbara Márquez Tirado, Elena Goicoechea de Jorge and their insightful review. The FH protein family emerges as a sophisticated network of proteins wielding significant influence over the complement alternative pathway (AP), steering susceptibility to a myriad of diseases including infectious, inflammatory, autoimmune, and degenerative conditions, as well as cancer.


💡 Comprising seven highly related proteins in humans—FH, Factor H-like 1 (FHL-1), and five Factor H-Related proteins (FHRs; FHR-1-5)—this protein family orchestrates a delicate dance between down-regulating and promoting AP activation. Recent discoveries have unveiled the molecular mechanisms dictating their biological roles and pathogenicity, emphasizing the critical balance between regulators and activators within the FH protein family. This equilibrium profoundly shapes the outcome of complement activation on cell surfaces.


🚀 The review navigates through the emerging roles of the FH protein family, elucidating their impact on the complement cascade and their involvement in the pathogenesis of complement-mediated diseases associated with AP dysregulation. The multifaceted functions of FH and FHRs play a pivotal role in modulating AP activation in various surface contexts, showcasing their ability to fine-tune complement regulation.


🌟 Beyond disease susceptibility, the FH protein family's relevance is underscored by its associations with common and rare genetic variations linked to diverse diseases—ranging from cancer and infectious diseases to autoimmune, renal, ocular, and neurodegenerative disorders. The exploration of genetic variants has not only advanced our understanding of their physiological role but has also shed light on the intricate pathogenic mechanisms leading to AP dysregulation and disease.


👏 Kudos to LAURA LUCIENTES CONTINENTE, Bárbara Márquez Tirado and Elena Goicoechea de Jorge for providing a comprehensive review, unraveling the biological roles of the FH protein family in health and disease. Stay tuned for more insights into the multifaceted functions of this intriguing protein family! 





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