Great question, its a typical problem for proteins with N-terminal and C-terminal processing, and considering the function of a protein it is relevant to all proteins that are modified by tagging with epitopes (FLAG, HA, c-myc...) or fluorescent proteins (GFP, YFP, RFP....). For a GPI-anchored protein I would seriously consider producing a recombinant secreted derivative in a eukaryotic expression system and raising specific antibodies that you can use to immunoprecipitate the native protein. However, I understand that this takes time and often people try epitope tagging first.

1) One approach would be to add the tag between the signal peptide and the mature portion of the protein, possibly with a glycine-serine linker after the epitope tag. I would also insert the first 3 aminoacids of the native portion of protein before the epitope, in order to avoid any changes to the signal peptide processing site. Also eukaryotic signal peptides are less sensitive towards the type of amino acids immediately after the cleavage site compared to prokaryotic signal peptides, it can happen that the epitope sequence is causing problems with signal peptide processing at the ER translocation pore. If the signal peptide is not cleaved, you end up with a membrane anchored protein that will probably not fold correctly. I would also try different tags to make sure you find one that works.

2) Alternatively, you could add the epitope tag before the processing site of the C-terminal transmembrane domain (the hydrophobic portion that is cleaved before the GPI-anchor takes over the function of membrane anchoring). But again, you have to make sure you don't upset the processing site, so I would insert it a few aminoacids further upstream and again I would try different epitope tags in parallel to find one that keeps the protein working normally.

In an case it is a tricky task and you have to approach it with trial and error. You are absolutely right to be worried about the removal of the epitopes if you simply insert at the N-terminus (before the signal peptide) or the C-terminus (after the hydrophobic transembrane domain, it is not going to work, don't even think of trying that. If you detect a protein, then it has not been processed properly and it is probably retained in the ER as a malfolded protein. If it is processed correctly, the tag is removed and you can't detect it. In all likelihood, both will happen, so you may see functionality in some bio-assay, and you may detect something with your anti epitope antibodies, but both methods report on different molecules so the results will be misleading. 

Thank you so much Jurgen! I think I'll try putting the tag in between the signal peptide and mature protein or the mature protein and the C-term processing site first. That was my initial thought too, but I've just never heard of anyone placing tags in the middle of a protein so I was hesitant to do it. 

Producing a recombinant derivative would take a lot time as you said and I'm a total novice to that field, so I hope I can avoid it! Also, I came across a method called QUICK while checking online for solutions. Have you ever used this/do you recommend it? 

https://www.nature.com/nmeth/journal/v3/n12/full/nmeth972.html

The QUICK method is not really quick, it is quite a sophisticated approach and you would have to setup everything from scratch. Regarding "placing tags in the middle of a protein", please remember that the N-terminal signal peptide does not really belong to the protein, it is just to be recognised by SRP, to be brought to the SEC61 pore on the ER for translocation, and it is cleaved off before translation and translocation is finished. The same is true for the C-terminal hydrophobic region that is cleaved prior to GPI-anchoring. So you are in fact adding a tag at the margins of the protein, hoping that the core remains functional. It is tricky and you can only know if it works when you try it. I wish you all the best, let me know if you are successful.

I know that it's not "quick". The protocol does seem quick labor intensive. I was just trying to find a way online to solve this issue and came across it. I'll try tagging first, but I wanted to learn about other options first. 

Yes, I'm aware of the signal peptide cleavage and ER/Golgi processing, so the tag would still be on the mature protein. I'll try placing the tag in a few different locations and hope one of them works! Thanks!