It might be difficult to determine whether the alleviated rosacea-like symptoms in Lrrc4 mutant mice are due to VIP inhibition or whether it is the combined PAC1/VPAC subtype receptor inhibition to play a role in improving symptoms, considering that VIP and PACAP both bind with high affinity to VPAC1, VPAC2 and PAC1 receptors, with the only difference that PACAP exhibits about 1000-fold higher affinity for PAC1 than VIP55,56, and VIPhyb has also been reported to suppress peptide histidine isoleucine (PHI) and PACAP in addition to VIP57,58. This evidence concerns the gene VIPR2 and rosacea.