Mutations in leucine-rich-repeats and immunoglobulin-like-domains 2 (LRIG2) or in heparanase 2 (HPSE2) cause urofacial syndrome, a devastating autosomal recessive disease of functional bladder outlet obstruction.
We focus on heparanase proteins and the peripheral nervous system, molecules and tissues that appear to be key players in the pathogenesis of UFS and therefore must also be critical for functional differentiation of healthy bladders.
In conclusion, heparanase 2 is an autonomic neural protein implicated in bladder emptying, but HPSE2 variants are uncommon in urinary diseases resembling UFS.