In this paper, we consider a system of reaction-diffusion equations in a domain consisting of two bulk regions separated by a thin layer with thickness of order and a periodic heterogeneous structure. The equations inside the layer depend on and the diffusivity inside the layer on an additional parameter γ ∈ [−1, 1]. On the bulk-layer interface, we assume a nonlinear Neumann-transmission condition depending on the solutions on both sides of the interface. For → 0, when the thin layer reduces to an interface Σ between two bulk domains, we rigorously derive macroscopic models with effective conditions across the interface Σ. The crucial part is to pass to the limit in the nonlinear terms, especially for the traces on the interface between the different compartments. For this purpose, we use the method of two-scale convergence for thin heterogeneous layers, and a Kolmogorov-type compactness result for Banach valued functions, applied to the unfolded sequence in the thin layer. 2010 Mathematics Subject Classification. 35B27, 35K57, 35K61, 80M40. Key words and phrases. Homogenization, nonlinear transmission conditions, reaction-diffusion systems, effective interface conditions, unfolding and averaging operator for thin heterogeneous layer, weak and strong two-scale convergence. The work of the first author was supported by the Center for Modelling and Simulation in the Biosciences (BIOMS) at the University of Heidelberg.