Sprouty-related, EVH1 domain-containing protein 2

SPRED2 (Sprouty-related, EVH1 domain-containing protein 2) is a negative regulator of Ras signaling that suppresses downstream mitogen-activated protein kinase activation (UniProt: Q7Z698). It functions by recruiting and translocating NF1 to the cell membrane, promoting GTP hydrolysis of active Ras to its inactive GDP-bound form. The protein also inhibits fibroblast growth factor-induced differentiation and TGF-β-mediated epithelial-to-mesenchymal transition in lens cells.

SPRED2 is primarily characterized in developmental and cellular signaling contexts. UniProt disease associations include Noonan syndrome 14, an autosomal recessive disorder featuring growth retardation, facial dysmorphism, cardiac defects, and variable intellectual deficits (UniProt: Q7Z698).

In Alzheimer's Disease, SPRED2 is down-regulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.61 across measured subcellular fractions (Chaparral AD proteomics). This reduction may reflect altered Ras-ERK signaling homeostasis in AD neuropathology, though the functional consequence remains to be determined.