PALD1 (paladin)

PALD1 (paladin, earlier KIAA1274) encodes a protein with a tyrosine phosphatase-like domain. UniProt lists no function text for the human protein (Q9ULE6) and HGNC names it 'phosphatase domain containing paladin 1', so what is known comes from animal work. Paladin was first picked out in screens for genes specific to blood vessels. In mice it sits in endosomes and the Golgi, binds vascular endothelial growth factor receptor 2 (VEGFR2) and removes a phosphate from the membrane lipid PI(4,5)P2; without it VEGFR2 is internalised more, ERK1/2 is over-activated and retinal vessels over-sprout (EMBO Reports 2021). Female mice lacking Pald1 develop emphysema-like lungs with endothelial cell death (Scientific Reports 2017). In the chick neural crest it behaves as an 'antiphosphatase': it shapes when Snail2 and Sox10 switch on and how the cells migrate, and mutating its predicted catalytic cysteines does not abolish that function (Developmental Biology 2012).

In cancer the evidence is thin. A 2022 study found paladin overexpressed in colon cancer, bound to the phosphatase SSH1, and needed for actin remodelling, cell migration and liver metastasis in mouse models (Oncogenesis 2022). Open Targets scores its association with non-Hodgkin lymphoma at 0.55. No drug targets it, no trial selects on it and it is not on any driver-gene list. The 2021 mouse work suggests that inhibiting paladin could be a way to tune VEGFR2 signalling when full blockade of the receptor is unwanted, an idea not yet tested in people.