In an elegant series of experiments, Yau and co-workers have proposed a mechanism for 3:1 CNGA:CNGB assembly that involves initial assembly of CNGA trimers 8 . They show that other three helix coiled coils, but not two helix or four helix coiled coils, could substitute for the CLZ domain of CNGA channels to reproduce normal heteromeric channel function and expression 20 . However, whereas we found that deletion of the CLZ domain causes an increase in CNGB1 incorporation in the channels, they showed that mutations in the CLZ domain decreased the incorporation of CNGB1 subunits 20 . Their results were explained by an assembly model where excess CNGA1 monomers outcompete CNGB1 monomers for channel incorporation. Instead, we propose that CNGB1 monomers outcompete CNGA1 monomers for channel incorporation owing to a high affinity association of CNGA1 and CNGB1 subunits. A high affinity association between CNGA and CNGB subunits has been previously proposed to explain the dependence of the CNGA:CNGB ratio in the surface membrane as a function of the ratio of their RNAs injected into the oocyte 9 . A high affinity association of CNGA1 and CNGB1 subunits also explains the large dominant negative effect of CNGB1 on deletion of the CLZ domain in CNGA1 (Fig. 2a) 21 . When the CLZ domain is deleted, the CNGA1 subunits preferentially interact with CNGB1 subunits, resulting in channels with multiple CNGB1 subunits that are not as efficiently expressed in the plasma membrane (Fig. 8b) . This defect has been proposed to underlie one form of inherited retinitis pigmentosa resulting from deletion of the last two heptad repeats of the CLZ domain of CNGA1 (refs 21,22) .