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Approximate Message Passing (AMP) is an efficient iterative parameter-estimation technique for certain high-dimensional linear systems with non-Gaussian distributions, such as sparse systems. In AMP, a so-called Onsager term is added to keep estimation errors approximately Gaussian. Orthogonal AMP (OAMP) does not require this Onsager term, relying instead on an orthogonalization procedure to keep the current errors uncorrelated with (i.e., orthogonal to) past errors. \LL{In this paper, we show the generality and significance of the orthogonality in ensuring that errors are "asymptotically independently and identically distributed Gaussian" (AIIDG).} This AIIDG property, which is essential for the attractive performance of OAMP, holds for separable functions. \LL{We present a simple and versatile procedure to establish the orthogonality through Gram-Schmidt (GS) orthogonalization, which is applicable to any prototype. We show that different AMP-type algorithms, such as expectation propagation (EP), turbo, AMP and OAMP, can be unified under the orthogonal principle.} The simplicity and generality of OAMP provide efficient solutions for estimation problems beyond the classical linear models. \LL{As an example, we study the optimization of OAMP via the GS model and GS orthogonalization.} More related applications will be discussed in a companion paper where new algorithms are developed for problems with multiple constraints and multiple measurement variables.